Late last year, a groundbreaking study out of the University of Ottawa was the first to demonstrate that Duchenne muscular dystrophy directly affects muscle stem cells.
“For nearly 20 years, we’ve thought that the muscle weakness observed in patients with Duchenne muscular dystrophy is primarily due to problems in their muscle fibres, but our research shows that it is also due to intrinsic defects in the function of their muscle stem cells,” said Dr. Michael Rudnicki, senior author of the study. “This completely changes our understanding of Duchenne muscular dystrophy and could eventually lead to far more effective treatments.”
Read our exclusive interview with Dr. Rudnicki:
A: It actually started because of an experiment looking at the effect of Wnt7a [a protein that stimulates and augments the repair process in muscle stem cells, and that also acts on muscle fibers to stimulate growth]. The control group without Wnt7a was very abnormal, and that provoked the whole series of experiments that led to this new discovery.
A: We are collaborating with Drs. Leanne Ward and Jodi Warman from the Children’s Hospital of Eastern Ontario (CHEO) to examine human biopsies from human Duchenne muscular dystrophy patients in order to confirm our findings [inhumans]. Recently, we were provided with photomicrographs that show polarized expression of dystrophin in human muscle stem cells. We fully anticipate our findings to be confirmed in human patients with Duchenne muscular dystrophy.
A: The design of any intervention—such as exon skipping, gene therapy or genomic editing—now must target both muscle stem cells and muscle fibers. This is already a consideration in the design of [therapeutic] interventions, but I think this point must be addressed even more strongly.
A: We have discovered that Wnt7a restores the function of DMD muscle stem cells and are undertaking experiments to test whether we can use Wnt7a as a therapeutic to treat DMD. We are also assessing other drugs that we have identified that act like Wnt7a. Our hope is that we can target muscle stem cells using a pharmacological intervention as a treatment that would complement gene correction approaches.
Dr. Michael Rudnicki (PhD, OC, FRSC) is the Senior Scientist in the Regenerative Medicine Program at the Ottawa Hospital Research Institute, the Director of the Regenerative Medicine Program and Sprott Centre for Stem Cell Research, a Professor in the Faculty of Medicine at the University of Ottawa, and the Scientific Director at the Stem Cell Network. Dr. Rudnicki holds the Canada Research Chair in Molecular Genetics.
Note: This article was republished from our annual report. Read the full report